Anticlastogenic effect of Ginkgo biloba extract in Graves' disease patients receiving radioiodine therapy.

BACKGROUND: Chromosomal damage, as assessed by clastogenic factors (CFs) and micronuclei (MN) appearance, after radioiodine therapy of Graves' disease has been reported. OBJECTIVE AND METHODS: Our objective was to evaluate the effect of Ginkgo biloba extract (EGb 761) supplementation on the time course (up to 120 d) of CFs and MN appearance in lymphocytes from patients with Graves' disease after iodine-131 ((131)I) therapy. Patients were randomly assigned to EGb 761 or placebo, in a blinded manner. RESULTS: In the placebo group, MN increased early (P < 0.001) after (131)I, peaking at the 21st day (P = 0.0003) and declining thereafter. In EGb 761-treated patients, MN increased early (P < 0.05), while returning toward baseline value thereafter. Therefore, mean MN increment was significantly higher in the placebo group as compared with EGb 761-treated patients (P < 0.01). Moreover, an early (P < 0.0001) and sustained (up to 35 d; P < 0.001) MN increase induced by CFs was observed in the placebo group. Conversely, in EGb 761-treated patients, MN increase induced by CFs never reached the statistical significance; therefore, the mean of the MN increments was significantly lower than in placebo (P < 0.05). A significant positive correlation between MN maximum increment and the bone marrow dose was observed in the placebo group only (P = 0.03). No significant difference was observed in clinical outcome between the two groups. CONCLUSIONS: EGb 761 supplementation neutralized genotoxic damage induced by radioiodine treatment, without affecting the clinical outcome. Although (131)I therapy is generally safe, our data suggest that Gingko biloba extracts may prevent genetic effects of radioiodine therapy for hyperthyroid Graves' disease.

Oxidative and genotoxic damage after radio-iodine therapy of Graves' hyperthyroidism.

PURPOSE: To evaluate genetic damage and oxidative stress following a single therapeutic dose of 131I in Graves' disease patients monitored up to 180 days after treatment. MATERIALS AND METHODS: Genetic damage induction was estimated as the increase in micronuclei in peripheral lymphocytes of patients. As indicators of radiogenic oxidative stress, vitamin E and lipoperoxide levels were assessed in the plasma of patients, as well as the release of plasmic clastogenic factors measured by the induction of micronuclei in vitro in peripheral lymphocytes of a healthy donor. RESULTS: Vitamin E depletion lasted at least 3 days and the basal level was restored within 7 days. No statistically significant variations were observed in lipoperoxide plasma levels. A sharp increase of micronuclei in the peripheral lymphocytes of patients was correlated (p < 0.001) with the release of clastogenic factor in the plasma. The highest micronucleus value was negatively correlated (p < 0.03) with the lowest vitamin E level observed in each patient. CONCLUSIONS: Micronuclei induction was the direct consequence not only of the energy deposition of 131I on the genetic material, but also of oxidative stress, likely via the release of clastogenic factor.

Chromosome aberrations in lymphocytes and clastogenic factors in plasma detected in Belarus children 10 years after Chernobyl accident.

In 1996, 10 years after Chernobyl accident, a cytogenetic analysis was carried out to assess whether chromosome aberrant cells (CA) were still detectable in the lymphocytes and clastogenic factors (CFs) were present in the plasma of children coming from Gomel (Belarus), one of the most heavily contaminated regions. Furthermore, the possible contribution of plasmatic CFs to the amount of CA was investigated. The presence of CA was examined in the lymphocytes from 29 thyroid tumour-affected children and 41 healthy children (local controls). Thirty healthy children living in Pisa (Italy) were enrolled in the study as additional controls from an uncontaminated area. No significant difference was observed between the two control groups, whereas a significantly increased frequency of CA was found in the tumour-affected children, as compared with Gomel and Pisa controls (chi 2-test, p < 0.001). However, when soil contamination level was taken into account, the chromosome type CA frequency observed in tumour-affected children coming from the more contaminated areas (> 4 Ci/km2) resulted significantly higher than that in other children, either affected or not (p = 0.003). The presence of CFs was analyzed on the plasma ultrafiltrate from 41 children. 7/10 (70%) plasma samples from tumour-affected children and 17/23 (74%) Gomel controls resulted to possess clastogenic activity irrespective of soil contamination levels. No activity was detected in the plasma of eight Pisa controls (0%). The difference between both Gomel groups and Pisa controls was highly significant (p = 0.002). A borderline, but not statistically significant correlation (p = 0.08) was observed between basal CA frequency and CF potency, which became significant (p = 0.03) when only chromosome type of aberrations was considered. We conclude that, although the presence of CFs in the plasma of these children might be partly responsible of the cytogenetic effects observed, the main source of damage has considered to be do to the previous and/or continuous exposure to environmental radiocontaminants. Tumour-affected children may represent a subset of the population either more sensitive to clastogenic damage or exposed to higher levels of contaminants.

Cytogenetic damage in lymphocytes of healthy and thyroid tumor-affected children from the Gomel region (Belarus).

During 1994, 19 thyroid tumor-affected children and 17 healthy children from the Gomel region, one of the areas most polluted by the Chernobyl fallout, were analysed for (i) the presence of in their urine and (ii) chromosome aberrations (CA) in circulating lymphocytes. They were compared with 35 healthy children from Pisa, Italy. Tumor-affected children showed significantly (p<0.05) higher levels in their urine as compared to healthy controls from the Gomel region. No radioactivity was found in urine from the Pisa controls. CA frequency was significantly higher in tumor-affected children compared to the Gomel controls, but was not significantly different between Gomel and Pisa controls. However, dicentric chromosomes were found in a significantly (p<0.01) greater proportion in both affected and healthy Gomel children (3.4 and 1.3/1000 cells, respectively) as compared to the Pisa controls (0.4/1000 cells). Multiple regression analysis showed that the proportion of cells with acentric fragments, dicentric and ring chromosomes was significantly correlated (p<0.05) with the amount of excreted in their urine. These findings suggest that children from the Gomel region were still being exposed to radionuclides, which makes it possible to study a dose-effect relationship.

Sister chromatid exchange and micronucleus frequency in human lymphocytes of 1,650 subjects in an Italian population: II. Contribution of sex, age, and lifestyle.

Sister chromatid exchange (SCE) and micronuclei (MN) analysis was carried out on 1,650 healthy individuals living in Pisa and in two nearby small cities, Cascina and Navacchio (Ca-Na). The effect of smoking on SCEs was linearly correlated with the number of cigarettes per day, and an increase of 7.3% SCEs was detectable for as few cigarettes as 1-10/day. Ex-smokers showed intermediate mean values of SCEs (8.09 +/- 1.88) in comparison with never smokers (7.54 +/- 1.61) and current smokers (8.45 +/- 1.94). Mean values of SCEs of ex-smokers decreased linearly with time of smoking cessation, reaching the mean values of never smokers within 8 years. The extent of SCE decrease was inversely proportional to the number of cigarettes previously smoked. No interaction between smoking habits and coffee or alcohol drinking on SCEs was observed. A borderline (P = 0.053) increase in mean SCE values in coffee drinkers (more than 3 cups/day) was found. The age effect on SCEs was remarkable in Ca-Na, but not in Pisa donors. Job type was not associated with significant modification of mean values of SCEs. Multiple logistic regression analysis revealed a statistically significant association between the proportion of high frequency cells (HCF) outliers and coffee consumption. Age and sex appeared to be by far the most important variables associated with modifications in MN frequency, which increased by 0.04 per thousand and 0.02 per thousand per year in males and females, respectively. Children and young donors (age < or = 40 years) showed lower MN frequency regardless of sex, whereas sex appeared to determine a significantly higher increase of MN only in females older than 40 years. In contrast, in males the MN rate by age tended to level off after the age of 30-50. MN frequencies of Pisa blue- and white-collar workers were statistically significantly higher than in students (+0.71 and +0.55 per thousand, respectively). Smoking did not determine any increase of MN frequency. A total lack of correlation (P = 0.913) between MN and SCEs was observed.

Cytogenetic monitoring of fishermen with environmental mercury exposure.

Due to high mercury levels in many Mediterranean aquatic organisms, people who live in this area and consume large amounts of seafood are exposed to a toxicological hazard. A group of 51 fishermen exposed to mercury through eating contaminated seafood from the northern Tyrrhenian Sea underwent cytogenetic monitoring. This work is part of a research project consisting of the evaluation of micronuclei (MN), chromosomal aberrations (CA) and sister-chromatid exchanges (SCE) in peripheral blood lymphocytes. Here we present data on mercury levels in blood and on micronucleus frequencies in peripheral blood lymphocytes of fishermen. The range of mercury concentrations in blood was 10.08-304.11 ng/g fresh weight, the average was 88.97 +/- 54.09 ng/g. Micronucleus frequency was defined with at least 2000 binucleated cells scored for each person; the average was 8.74 +/- 2.56 expressed on 1000 binucleated cells. A statistical correlation was found between MN frequency and total mercury concentration in blood (p = 0.00041, r = 0.674), as well as between MN frequency and age (p = 0.017). No other parameters taken into account correlated with MN frequency.